In recent years, a biomolecule measuring device using a semiconductor technique has been focused on attention. Patent Document 1 has described a DNA sequencer that determines a base sequence of a deoxyribonucleic acid (DNA) at high speed and low cost by using a pH sensor array (semiconductor sensor) manufactured by the semiconductor technique. The semiconductor sensor can quantify a reaction between a target biomolecular sample and a reagent by using the strength of an electric signal. For this reason, this method is advantageous in terms of costs without the necessity of an expensive fluorescent reagent as conventionally used. Moreover, since sensors of several millions to several hundred millions can be integrated on a single semiconductor substrate by a micro-processing technique of a semiconductor and can measure in parallel, the throughput of the measurement can be easily improved.
One of the semiconductor sensors that are particularly used so often in the field of the biomolecule measuring device is an ion sensitive field effect transistor (Ion Sensitive Field Effect Transistor: hereinafter, referred to as ISFET). The ISFET is a device for measuring an interface electric potential induced on an ion sensitive layer.
In Patent Document 1, by using the ISFET, a change in the hydrogen ion concentration caused by an elongation reaction of DNA due to the reagent is measured. There are four types of bases forming the DNA, and the type of the base can be specified from the change in the hydrogen ion concentration by using a reagent that reacts only with a specific base to generate hydrogen ions. Here, the four types of bases are adenine, thymine, cytosine and guanine.
The voltage change due to a change in hydrogen ion concentration can be theoretically found from an equation referred to as Nernst equation. For example, at 25° C., the voltage change is about 59 mV/pH. This change (variation) changes the gate voltage of the ISFET so that the output current of the ISFET changes. Practically, the voltage change with respect to the change in the hydrogen ion concentration is lower than its theoretical value, and becomes about several 10 mV per pH. The change in hydrogen ion concentration caused by the above-described elongation reaction of DNA is about 0.1 mV in terms of the pH change, although it also depends on the number of DNA chains causing the reaction, the size of space causing the reaction, and the reagent. Therefore, the change in the output signal of the ISFET is extremely small.
In order to solve this problem, increase in the sensitivity of the ISFET has been studied. As an example of this, a technique described in Patent Document 2 is cited. In Patent Document 2, a large number of ISFETs are arranged in an array form, and FIG. 75F of the document shows a unit cell for detecting the change in the hydrogen ion concentration by a reference numeral 75F1. This unit cell 75F1 has a function of increasing the sensitivity. In FIG. 75F, a portion indicated as ISFET represents an ISFET circuit, and the ISFET is configured by an ion sensitive layer (portion) 75F6 and an MOSFET (transistor) 75F2 whose gate is connected with the ion sensitive layer. In this drawing, a reference numeral 75F3 indicates an MOSFET to which a bias current is applied, and a reference numeral 75F4 is an MOSFET to be connected to an output signal wire 75F7 (Column Bus). Moreover, in this drawing, “Row Select” represents a signal wire for use in selecting the unit cell 75F1.
In Patent Document 2, the sensitivity of the ISFET is increased by the MOSFET 75F5. That is, the output of the MOSFET 75F2 is inputted to the gate of the MOSFET 75F5. By the change in the hydrogen ion concentration, the gate voltage of an ISFET configured by the MOSFET 75F2 and the ion sensitive layer 75F6 is changed. By this change, the output current of the ISFET is changed. This change is amplified once by the MOSFET 75F5. That is, the small change in the ISFET output current due to the change in hydrogen ion concentration is amplified. After the amplification, the resulting current is outputted to an output signal line 75F7 through the MOSFET 75F4. Thus, the sensitivity of the ISFET can be increased.
Meanwhile, existence of a charge other than being derived from the measurement target ion in the device of the ISFET causes a measurement error. In general, the semiconductor process has such a problem that a charge tends to be easily accumulated in the device since a plasma processing and an ion injection are performed at the time of manufacturing a device. In relation to this problem, Non-Patent Document 1 has described that charges are accumulated on interfaces among an ion sensitive layer, a protective layer and electrodes as well as on a floating electrode and a gate oxide film. Non-Patent Document 1 has described that the threshold voltage of the ISFET is offset by about ±10 V due to such charge accumulation.
If such an offset exists, the offset is also amplified as it is in the configuration as shown in FIG. 75F of Patent Document 2.
As a conventional technique for removing such an offset, Patent Document 1 has described a method of extracting the charge to the outside of the device by giving an energy thereto by irradiating it with ultraviolet rays. Moreover, Non-Patent Document 2 has described that the irradiation with ultraviolet rays needs to be performed for a long period of time such as 10 hours. Furthermore, as another method, Non-Patent Document 3 has described that the change in the threshold voltage due to the captured charges can be reduced by injection of hot electrons.